It is known that some macromolecular substances have the effect of potentiating immunological response in vivo. Thus, it is well-known that a water-insoluble residue recovered from the products obtained by autolysis or protease-treatment of yeast cell walls takes part in the immunological defense mechanism of a living animal and exhibits a protective action against bacterial infections. An example of such water-insoluble residue is a substance designated as "Zymosan" [see Nagy et al., Archivo Italiano di Patologia e Clinica der Tumori, XIV, Fasc. 3.about.4, pages 29.about.35 (1971); F. W. Fitzpatrick, F. I. Dicarlo, Ann. New York Acad. Sci., 118 (4), pages 233.about.262 (1964)]. In the 25th General Meeting of the Japan Chemotherapy Society (see Summary Report, page 157, issued on June 11, 1976), it is proposed that Zymosan is used as a standard drug to evaluate the activity of Picibanil to protect against the infection by some bacteria of genus Staphylococus.
Reference is further made to Japanese Patent KOKAI (Preliminary Publication) No. 70809/76 and No. 29215/76, which disclose immunopotentiating effect of a material constituting yeast cell wall hydrolyzate. Japanese Patent KOKAI No. 27101/80 discloses prophylactic and therapeutic effects on infectious diseases of KS-2-A substance which is produced by culturing a mycelium.
In recent years, it has been reported that N-acetylmuramyl-L-alanyl-D-isoglutamine (Japanese Patent KOKAI No. 41211/77) and N-acetylmuramyl-L-alanyl-D-glutamine (Japanese Patent KOKAI No. 44223/77) possess a high adjuvant effect as water-soluble, low-molecular weight immunopotentiator. It has also been found that orthobenzoic acid oxide exhibits a protective activity against bacterial infections (Chem. Pharm. Bull., 2143 (1977), Japanese Patent KOKAI No. 41041/76 and Japanese Patent KOKAI No. 12141/77) and that a certain aziridine derivative provides an increased degree of resistance to bacterial infections (Japanese Patent KOKAI No. 111563/77).
As described above, there are a variety of compounds derived through a synthetic route, which have already been proposed as protective agent against bacterial infections, but all these compounds are entirely different in chemical nature from the new compound according to this invention. Thus, the orthobenzoic acid oxide is of skeleton of an aromatic ring (Japanese Patent KOKAI No. 41041/76 and No. 12141/77) and the aziridine derivative is of skeleton of three-membered ring (Japanese Patent KOKAI No. 111563/77). Examples of low-molecular weight immunopotentiator already proposed are 4-imino-1,3-diazobicyclo[3,1,0]hexan-2-one (Japanese Patent KOKAI No. 10290/77), N-2-(6-hydroxybenzothiazolyl)-N'-substituted or unsubstituted phenylurea (Japanese Patent KOKAI No. 59860/76) and pyrrolidine derivatives (Japanese Patent KOKAI No. 98299/76). Examples of higher-molecular weight immunopotentiator are fatty acid esters of fructose and sucrose (Japanese Patent KOKAI No. 29291/76), fatty acid esters of glucose and trehalose (Japanese Patent KOKAI No. 29292/76), 6,6'-dimycolate of trehalose (Cancer Imm. Immunother, 1, 227 (1976)) and 6-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (IUPAC A.P. 6C2-14 (1977)).
We have now prepared a new polymeric compound derived from the reaction of ribostamycin with crotonoyl chloride and found that it has no antibacterial activity in vitro and is not metaborized in vivo into a substance having an antibacterial activity, but unexpectedly it exhibits a protective activity against bacterial infection in vivo.